"Studying Bovine Mastitis: How Can That Help Us Understand Human Toxic-Shock Syndrome and Staphylococcal Food Poisoning"

Abstract: Staphylococcus aureus is an important pathogenic bacterium for humans as well as a variety of animals. Recently, it has received renewed public attention because of the occurrence of highly virulent strains within communities that are resistant to methicillin. In a typical year, S. aureus causes up to 9 million treated human infections with an economic impact of nearly $7 million. In addition, S. aureus is the leading agent of bovine mastitis, an infectious disease that causes $2 billion in lost revenue to the dairy industry in the U.S. alone.

We have been interested in understanding the role of protein exotoxins produced by staphylococci and related organisms. In particular, a group of toxins known as superantigens are recognized for their large-scale activation of the immune system. This property is responsible for their ability to cause a serious disease known as toxic shock syndrome as well as staphylococcal food poisoning. Interestingly, many strains of S. aureus, including those that colonize humans and animals, produce one or more superantigens. Considering their widespread occurrence, we have been exploring the hypothesis that 'superantigen production by bacteria causes an effect on the immune system that down regulates local immunity and promotes colonization and/or persistence'.

Using a variety of animal models, we have confirmed that the toxins repress the immune response, including to S. aureus. Several cell types, consistent with immunosuppression, are induced in vitro and in vivo. In addition, bacteria that express superantigens are more able to colonize and cause infections compared to isogenic strains in which the toxin genes are deleted. Combined, these results indicate that a selective advantage is provided to bacteria capable of expressing superantigens. The well-known ability of superantigens to induce severe shock-like symptoms in toxic shock syndrome and other adverse effects are likely secondary effects of the immunosuppression. The occurrence of these severe secondary effects also suggests that S. aureus likely acquired these toxin genes relatively recently. If so, it is also likely that further co-evolution of the bacteria with their respective hosts will lead to toxins that are more efficient at inducing immunosuppression and less likely to induce shock.

Original url: http://www.uidaho.edu/class/mric/archives/pre-2010/fall2008/bohach